{[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid

• ChemBase ID: 1004
• Molecular Formular: C7H9ClO6P2S
• Molecular Mass: 318.608282
• Monoisotopic Mass: 317.92835995
• SMILES: Clc1ccc(SC(P(=O)(O)O)P(=O)(O)O)cc1
• Canonical SMILES: Clc1ccc(cc1)SC(P(=O)(O)O)P(=O)(O)O
• InChI: InChI=1S/C7H9ClO6P2S/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14/h1-4,7H,(H2,9,10,11)(H2,12,13,14)
• InChIKey: DKJJVAGXPKPDRL-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: {[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid
• IUPAC Traditional name: tiludronate
• Brand Name: Skelid
• Synonyms: Acide tiludronique [INN-French]; Acido tiludronico [INN-Spanish]; Acidum tiludronicum [INN-Latin]; Tiludronate disodium; Tiludronic acid; Tiludronic Acid Disodium Salt; Tiludronate

Database IDs

• CAS Number: 89987-06-4
• PubChem SID: 46505302; 160964467
• PubChem CID: 60937

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.0278608
• H Acceptors: 6
• H Donor: 4
• LogD (pH = 5.5): -3.275569
• LogD (pH = 7.4): -3.4738543
• Log P: 1.3220819
• Molar Refractivity: 65.1071 cm^3
• Polarizability: 25.871422 Å^3
• Polar Surface Area: 115.06 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.62
• LOG S: -1.66
• Solubility (Water): 6.97e+00 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): -0.6

DETAILS

DrugBank - DB01133

• Drug Groups: approved
• Description: Tiludronate is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.
• Indication: For treatment of Paget's disease of bone (osteitis deformans).
• Pharmacology: Tiludronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and clodronate. Tiludronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the tiludronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface.
• Toxicity: Based on the known action of tiludronate, hypocalcemia is a potential consequence of overdose. In one patient with hypercalcemia of malignancy, intravenous administration of high doses (800 mg/day total dose, 6 mg/kg/day for 2 days) was associated with acute renal failure and death.
• Affected Organisms: Humans and other mammals
• Biotransformation: In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.
• Absorption: The mean oral bioavailability in healthy male subjects is 6% after an oral dose equivalent to 400 mg tiludronic acid administered after an overnight fast and 4 hours before a standard breakfast. In single-dose studies, bioavailability was reduced by 90% when an oral dose equivalent to 400 mg tiludronic acid was administered with, or 2 hours after, a standard breakfast compared to the same dose administered after an overnight fast and 4 hours before a standard breakfast.
• Half Life: Half-life in healthy subjects is 50 hours following administration of a 400 mg single oral dose. Half-life in pagetic patients is about 150 hours following administration of 400 mg tiludronate a day for 12 days. In patients with renal insufficiency (creatinine clearance between 11 and 18 mL per minute [mL/min]), half-life is 205 hours from plasma after administration of a single, oral dose equivalent to 400 mg tiludronate.
• Protein Binding: Approximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.
• Elimination: The principal route of elimination of tiludronic acid is in the urine.
• Clearance: * renal cl=10 mL/min [IV administration of 20-mg dose]
• References: Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T: A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995 Aug;17(2):137-44. [Pubmed] ; Rogers MJ: New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9(32):2643-58. [Pubmed] ; Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T: A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995 Aug;17(2):137-44. Pubmed
• Rogers MJ: New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9(32):2643-58. Pubmed
• Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. Pubmed